MicroRNA-210 Controls Mitochondrial Metabolism during Hypoxia by Repressing the Iron-Sulfur Cluster Assembly Proteins ISCU1/2
Open accessAbstract
Repression of mitochondrial respiration represents an evolutionarily ancient cellular adaptation to hypoxia and profoundly influences cell survival and function; however, the underlying molecular mechanisms are incompletely understood. Primarily utilizing pulmonary arterial endothelial cells as a representative hypoxic cell type, we identify the iron-sulfur cluster assembly proteins (ISCU1/2) as direct targets for repression by the hypoxia-induced microRNA-210 (miR-210). ISCU1/2 facilitate the assembly of iron-sulfur clusters, prosthetic groups that are critical for electron transport and mitochondrial oxidation-reduction reactions. Under in vivo conditions of upregulating miR-210 and repressing ISCU1/2, the integrity of iron-sulfur clusters is disrupted. In turn, by repressing ISCU1/2 during hypoxia, miR-210 decreases the activity of prototypical iron-sulfur proteins controlling mitochondrial metabolism, including Complex I and aconitase. Consequently, miR-210 represses mitochondrial respiration and associated downstream functions. These results identify important mechanistic connections among microRNA, iron-sulfur cluster biology, hypoxia, and mitochondrial function, with broad implications for cellular metabolism and adaptation to cellular stress.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HIF-1-mediated transcriptional upregulation of miR210 specifically inhibits Fe-S complex formation to alter mitochondrial bioenergetics and ROS production (Pasteur effect).
“The coordinate metabolic changes caused by HIF-1 that alter mitochondrial function are attributable, in part, to the HIF-1-mediated transcriptional upregulation of microRNA 210 (miR210), which specifically inhibits Fe-S complex formation to alter mitochondrial bioenergetics and ROS production (Pasteur effect) (69).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
During normoxia, forced expression of miR210 causes an increase in ROS generation.
“Interestingly, during normoxia, forced expression of miR210 caused an increase in ROS generation (69, 81), possibly due to deficiencies in complex I that may promote electron leak in the presence of molecular oxygen.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
Enhanced ROS production is not a sustained event in hypoxia.
“Nonetheless, experimental evidence suggests that enhanced ROS production is not a sustained event in hypoxia (69, 385).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
Within mitochondria, miR-210 targets regulatory proteins that assist in the assembly of the complexes of the electron transport chain, and suppresses respiration.
“Within mitochondria it targets regulatory proteins that assist in the assembly of the complexes of the electron transport chain, and suppresses respiration (103, 108).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [103]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601 · see citing works
RetractedKim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905 · see citing works
Iron-sulfur clusters: nature's modular, multipurpose structures
Beinert, H., Holm, R. H., & Münck, E. (1997) · Science · doi:10.1126/science.277.5326.653 · Cited by 1,944 · see citing works
HIF-1 Regulates Cytochrome Oxidase Subunits to Optimize Efficiency of Respiration in Hypoxic Cells
Fukuda, R., Zhang, H., Kim, J.-W., Shimoda, L., Dang, C. V., & Semenza, G. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.047 · Cited by 1,225 · see citing works
Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., Garcia, J. G. N., & Semenza, G. L. (2005) · Blood · doi:10.1182/blood-2004-07-2958 · Cited by 1,154 · see citing works
A MicroRNA Signature of Hypoxia
Kulshreshtha, R., Ferracin, M., Wojcik, S. E., Garzon, R., Alder, H., Agosto-Perez, F. J., Davuluri, R., Liu, C.-G., Croce, C. M., Negrini, M., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01395-06 · Cited by 1,055 · see citing works
Hypoxia-Induced Pulmonary Vascular Remodeling
Stenmark, K. R., Fagan, K. A., & Frid, M. G. (2006) · Circulation Research · doi:10.1161/01.res.0000243584.45145.3f · Cited by 1,001 · see citing works
Fasanaro, P., D'Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M. C., & Martelli, F. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800731200 · Cited by 912 · see citing works
hsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer
Camps, C., Buffa, F. M., Colella, S., Moore, J., Sotiriou, C. P., Sheldon, H., Harris, A. L., Gleadle, J., & Ragoussis, J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1755 · Cited by 658 · see citing works
Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells
Seagroves, T. N., Ryan, H. E., Lu, H., Wouters, B. G., Knapp, M., Thibault, P., Laderoute, K. R., & Johnson, R. S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3436-3444.2001 · Cited by 634 · see citing works
Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1
Semenza, G. L. (2007) · Biochemical Journal · doi:10.1042/bj20070389 · Cited by 541 · see citing works
Hypoxic pulmonary vasoconstriction
Moudgil, R., Michelakis, E. D., & Archer, S. L. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00733.2004 · Cited by 452 · see citing works
MicroRNA regulation of DNA repair gene expression in hypoxic stress
Crosby, M. E., Kulshreshtha, R., Ivan, M., & Glazer, P. M. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2516 · Cited by 437 · see citing works
Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells
Mann, G. E., Yudilevich, D. L., & Sobrevia, L. (2003) · Physiological Reviews · doi:10.1152/physrev.00022.2002 · Cited by 430 · see citing works
Vascular tumors in livers with targeted inactivation of the von Hippel–Lindau tumor suppressor
Haase, V. H., Glickman, J. N., Socolovsky, M., & Jaenisch, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1583 · Cited by 421 · see citing works
Mitochondrial respiratory chain inhibitors induce apoptosis
Wolvetang, E. J., Johnson, K. L., Krauer, K. G., Ralph, S. J., & Linnane, A. W. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)80380-3 · Cited by 398 · see citing works
Iron–sulfur cluster biogenesis and human disease
Rouault, T. A., & Tong, W. H. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.05.008 · Cited by 387 · see citing works
Sowter, H., Raval, R. R., Moore, J. W., Ratcliffe, P. J., & Harris, A. L. (2003) · PubMed · Cited by 374 · see citing works
miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer
Giannakakis, A., Sandaltzopoulos, R., Greshock, J. D., Liang, S., Huang, J., Hasegawa, K., Li, C., O’Brien-Jenkins, A., Katsaros, D., Weber, B. L., et al. (2008) · Cancer Biology & Therapy · doi:10.4161/cbt.7.2.5297 · Cited by 345 · see citing works
Lazazzera, B. A., Beinert, H., Khoroshilova, N., Kennedy, M. C., & Kiley, P. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.5.2762 · Cited by 317 · see citing works
Wang, V., Davis, D. A., Haque, M., Huang, E. L., & Yarchoan, R. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4130 · Cited by 309 · see citing works
Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure
Minamishima, Y. A., Moslehi, J., Bardeesy, N., Cullen, D., Bronson, R. T., & Kaelin, W. G. (2008) · Blood · doi:10.1182/blood-2007-10-117812 · Cited by 294 · see citing works
Tong, W.-H., & Rouault, T. A. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.003 · Cited by 294 · see citing works
A microRNA component of the hypoxic response
Kulshreshtha, R., Davuluri, R. V., Calin, G. A., & Ivan, M. (2008) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402310 · Cited by 273 · see citing works
PHDs overactivation during chronic hypoxia “desensitizes” HIFα and protects cells from necrosis
Ginouvès, A., Ilc, K., Cámara, N. M., Pouysségur, J., & Berra, E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705680105 · Cited by 256 · see citing works
Mammalian Tissue Oxygen Levels Modulate Iron-Regulatory Protein Activities in Vivo
Meyron‐Holtz, E. G., Ghosh, M. C., & Rouault, T. A. (2004) · Science · doi:10.1126/science.1103786 · Cited by 246 · see citing works
VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400
Young, A. P., Schlisio, S., Minamishima, Y. A., Zhang, Q., Li, L., Grisanzio, C., Signoretti, S., & Kaelin, W. G. (2008) · Nature Cell Biology · doi:10.1038/ncb1699 · Cited by 239 · see citing works
Mochel, F., Knight, M. A., Tong, W.-H., Hernandez, D. G., Ayyad, K., Taivassalo, T., Andersen, P. M., Singleton, A., Rouault, T. A., Fischbeck, K. H., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.12.012 · Cited by 208 · see citing works
Organization of Iron-Sulfur Clusters in Respiratory Complex I
Hinchliffe, P., & Sazanov, L. A. (2005) · Science · doi:10.1126/science.1113988 · Cited by 197 · see citing works
Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells
Tong, W., & Rouault, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5692 · Cited by 194 · see citing works
Hypoxia response and microRNAs: no longer two separate worlds
Ivan, M., Harris, A. L., Martelli, F., & Kulshreshtha, R. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00398.x · Cited by 193 · see citing works
Thierbach, R., Schulz, T. J., Isken, F., Voigt, A., Mietzner, B., Drewes, G., von Kleist-Retzow, J.-C., Wiesner, R. J., Magnuson, M. A., Puccio, H., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi410 · Cited by 127 · see citing works
Frataxin, Iron–Sulfur Clusters, Heme, ROS, and Aging
Napoli, E., Taroni, F., & Cortopassi, G. A. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.506 · Cited by 96 · see citing works
Aisenberg, A. C., & Potter, V. R. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)65001-x · Cited by 70 · see citing works
Endothelial cell tolerance to hypoxia. Potential role of purine nucleotide phosphates.
Tretyakov, A. V., & Farber, H. W. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117721 · Cited by 55 · see citing works
Mitochondria and Hypoxia‐induced Gene Expression Mediated by Hypoxia‐inducible Factors
Chavez, A., Miranda, L. F., Pichiule, P., & Chavez, J. C. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.021 · Cited by 43 · see citing works
Flagged first, then by citations
1 of the 37 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond
Lee, P., Chandel, N. S., & Simon, M. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0227-y · Cited by 1,272 · see citing works
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335 · see citing works
Antioxidant responses and cellular adjustments to oxidative stress
Espinosa-Diez, C., Miguel, V., Mennerich, D., Kietzmann, T., Sánchez-Pérez, P., Cadenas, S., & Lamas, S. (2015) · Redox Biology · doi:10.1016/j.redox.2015.07.008 · Cited by 1,046 · see citing works
Advances in Hypoxia-Inducible Factor Biology
Choudhry, H., & Harris, A. L. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.005 · Cited by 873 · see citing works
Hypoxia-Inducible Factors: Master Regulators of Cancer Progression
Schito, L., & Semenza, G. L. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.10.016 · Cited by 962 · see citing works
MicroRNA Functions in Stress Responses
Leung, A. K. L., & Sharp, P. A. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.027 · Cited by 843 · see citing works
Lu, J., Tan, M., & Cai, Q. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.04.001 · Cited by 800 · see citing works
Mitochondrial reactive oxygen species and cancer
Sullivan, L. B., & Chandel, N. S. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-17 · Cited by 799 · see citing works
Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717 · see citing works
Mitochondrial composition and function under the control of hypoxia
Fuhrmann, D. C., & Brüne, B. (2017) · Redox Biology · doi:10.1016/j.redox.2017.02.012 · Cited by 646 · see citing works
Prabhakar, N. R., & Semenza, G. L. (2012) · Physiological Reviews · doi:10.1152/physrev.00030.2011 · Cited by 641 · see citing works
Hypoxia-Inducible Factor 1 and Cardiovascular Disease
Semenza, G. L. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170322 · Cited by 608 · see citing works
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
Self-citationHypoxia-inducible factors: cancer progression and clinical translation
Wicks, E. E., & Semenza, G. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci159839 · Cited by 600 · see citing works
Iron and cancer: recent insights
Manz, D. H., Blanchette, N. L., Paul, B. T., Torti, F. M., & Torti, S. V. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13008 · Cited by 507 · see citing works
Metabolic zonation of the liver: The oxygen gradient revisited
Kietzmann, T. (2017) · Redox Biology · doi:10.1016/j.redox.2017.01.012 · Cited by 499 · see citing works
Reciprocal Regulation of HIF-1α and LincRNA-p21 Modulates the Warburg Effect
Yang, F., Zhang, H., Mei, Y., & Wu, M. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.11.004 · Cited by 510 · see citing works
Mitochondria and Endothelial Function
Kluge, M. A., Fetterman, J. L., & Vita, J. A. (2013) · Circulation Research · doi:10.1161/circresaha.111.300233 · Cited by 508 · see citing works
Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target
Infantino, V., Santarsiero, A., Convertini, P., Todisco, S., & Iacobazzi, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115703 · Cited by 510 · see citing works
Semenza, G. L. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.08.006 · Cited by 484 · see citing works
MicroRNA-210 as a Novel Therapy for Treatment of Ischemic Heart Disease
Hu, S., Huang, M., Li, Z., Jia, F., Ghosh, Z., Lijkwan, M. A., Fasanaro, P., Sun, N., Wang, X., Martelli, F., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.928424 · Cited by 462 · see citing works
microRNA Therapeutics in Cancer — An Emerging Concept
Shah, M., Ferrajoli, A., Sood, A. K., Lopez‐Berestein, G., & Călin, G. A. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.09.017 · Cited by 454 · see citing works
Vascular Endothelial Growth Factor Signaling in Hypoxia and Inflammation
Ramakrishnan, S., Anand, V., & Roy, S. (2014) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-014-9531-7 · Cited by 445 · see citing works
Baggish, A. L., Hale, A., Weiner, R. B., Lewis, G. D., Systrom, D., Wang, F., Wang, T. J., & Chan, S. Y. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.213363 · Cited by 431 · see citing works
Self-citationHypoxia. 2. Hypoxia regulates cellular metabolism
Wheaton, W. W., & Chandel, N. S. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00485.2010 · Cited by 426 · see citing works
Du, J., Wang, T., Li, Y., Zhou, Y., Wang, X., Yu, X., Ren, X., An, Y., Wu, Y., Sun, W., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.12.011 · Cited by 487 · see citing works
Puisségur, M.-P., Mazure, N. M., Bertero, T., Pradelli, L. A., Grosso, S., Robbe-Sermesant, K., Maurin, T., Lebrigand, K., Cardinaud, B., Hofman, V., et al. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.119 · Cited by 422 · see citing works
Ghosh, G., Subramanian, I. V., Adhikari, N., Zhang, X., Joshi, H. P., Basi, D. L., Chandrashekhar, Y., Hall, J. L., Roy, S., Zeng, Y., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42980 · Cited by 417 · see citing works
Nagao, A., Kobayashi, M., Koyasu, S., Chow, C. C. T., & Harada, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020238 · Cited by 411 · see citing works
Signal Transduction by Mitochondrial Oxidants
Finkel, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.271999 · Cited by 390 · see citing works
HIF-1α protects against oxidative stress by directly targeting mitochondria
Li, H.-S., Zhou, Y., Li, L., Li, S., Long, D., Chen, X., Zhang, J., Feng, L., & Li, Y. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101109 · Cited by 392 · see citing works
MiR-210 – micromanager of the hypoxia pathway
Huang, X., Le, Q., & Giaccia, A. J. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.03.004 · Cited by 376 · see citing works
Garofano, L., Migliozzi, S., Oh, Y. T., D’Angelo, F., Najac, R. D., Ko, A., Frangaj, B., Caruso, F. P., Yu, K., Yuan, J., et al. (2021) · Nature Cancer · doi:10.1038/s43018-020-00159-4 · Cited by 363 · see citing works
Tello, D., Balsa, E., Acosta‐Iborra, B., Fuertes-Yebra, E., Elorza, A., Ordóñez, Á., Corral-Escariz, M., Soro-Arnáiz, I., López-Bernardo, E., Perales‐Clemente, E., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.008 · Cited by 369 · see citing works
Semenza, G. L. (2016) · The EMBO Journal · doi:10.15252/embj.201695204 · Cited by 369 · see citing works
Chan, Y. C., Banerjee, J., Choi, S. Y., & Sen, C. K. (2011) · Microcirculation · doi:10.1111/j.1549-8719.2011.00154.x · Cited by 364 · see citing works
MicroRNA-210: A unique and pleiotropic hypoxamir
Chan, S. Y., & Loscalzo, J. (2010) · Cell Cycle · doi:10.4161/cc.9.6.11006 · Cited by 357 · see citing works
Self-citationReactive oxygen species, nutrition, hypoxia and diseases: Problems solved?
Görlach, A., Dimova, E. Y., Petry, A., Martı́nez-Ruiz, A., Hernansanz‐Agustín, P., Rolo, A. P., Palmeira, C. M., & Kietzmann, T. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.016 · Cited by 351 · see citing works
Regulation of Metabolism by Hypoxia-Inducible Factor 1
Semenza, G. L. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010678 · Cited by 342 · see citing works
Favaro, E., Ramachandran, A., McCormick, R., Gee, H., Blancher, C., Crosby, M., Devlin, C., Blick, C., Buffa, F., Li, J.-L., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010345 · Cited by 324 · see citing works
“Recently, ISCU has been identified as a miR-210 target also in normal pulmonary endothelial cells [20], where it contributes to the Pasteur effect and controls the level of ROS production in hypoxia, suggesting its potential adaptive role to hypoxia in the context of pulmonary endothelium.”
BackgroundGameiro, P. A., Yang, J., Metelo, A. M., Pérez-Carro, R., Baker, R., Wang, Z., Arreola, A., Rathmell, W. K., Olumi, A., López-Larrubia, P., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.02.002 · Cited by 325 · see citing works
The Metabolic Theory of Pulmonary Arterial Hypertension
Paulin, R., & Michelakis, E. D. (2014) · Circulation Research · doi:10.1161/circresaha.115.301130 · Cited by 317 · see citing works
Buffa, F. M., Camps, C., Winchester, L. M., Snell, C. E., Gee, H. E., Sheldon, H., Taylor, M., Harris, A. L., & Ragoussis, J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0489 · Cited by 309 · see citing works
Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer
Bao, M. H.-R., & Wong, C. C.-L. (2021) · Cells · doi:10.3390/cells10071715 · Cited by 316 · see citing works
Masson, N., & Ratcliffe, P. J. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-3 · Cited by 296 · see citing works
miR‐210: More than a silent player in hypoxia
Devlin, C. M., Greco, S., Martelli, F., & Ivan, M. (2011) · IUBMB Life · doi:10.1002/iub.427 · Cited by 289 · see citing works
The EGLN-HIF O 2 -Sensing System: Multiple Inputs and Feedbacks
Ivan, M., & Kaelin, W. G. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.002 · Cited by 273 · see citing works
Hypoxia: A master regulator of microRNA biogenesis and activity
Nallamshetty, S., Chan, S. Y., & Loscalzo, J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.022 · Cited by 281 · see citing works
Self-citationBiswas, S., Roy, S., Banerjee, J., Hussain, S.-R. A., Khanna, S., Meenakshisundaram, G., Kuppusamy, P., Friedman, A., & Sen, C. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001653107 · Cited by 272 · see citing works
Chen, R., Lai, U. H., Zhu, L., Singh, A., AlKataan, M. A. A., & Forsyth, N. R. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00132 · Cited by 271 · see citing works
MicroRNA-21 Integrates Pathogenic Signaling to Control Pulmonary Hypertension
Parikh, V. N., Jin, R. C., Rabello, S., Gulbahce, N., White, K., Hale, A., Cottrill, K. A., Shaik, R. S., Waxman, A. B., Zhang, Y., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.060269 · Cited by 264 · see citing works
Self-citationInterplay between epigenetics and metabolism in oncogenesis: mechanisms and therapeutic approaches
Wong, C. C., Qian, Y., & Yu, J. Q. (2017) · Oncogene · doi:10.1038/onc.2016.485 · Cited by 260 · see citing works
The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system
Kietzmann, T., Petry, A., Shvetsova, A., Gerhold, J. M., & Görlach, A. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13792 · Cited by 253 · see citing works
Guo, W., Qiu, Z., Wang, Z., Wang, Q., Tan, N., Chen, T., Chen, Z., Huang, S., Gu, J., Li, J., et al. (2015) · Hepatology · doi:10.1002/hep.27929 · Cited by 252 · see citing works
Qiu, G., Jin, M., Dai, J., Sun, W., Feng, J., & Jin, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.05.002 · Cited by 245 · see citing works
The Warburg effect: Insights from the past decade
Upadhyay, M., Samal, J., Kandpal, M., Singh, O. V., & Vivekanandan, P. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.11.003 · Cited by 245 · see citing works
MIR-210 modulates mitochondrial respiration in placenta with preeclampsia
Muralimanoharan, S., Maloyan, A., Mele, J., Guo, C., Myatt, L. G., & Myatt, L. (2012) · Placenta · doi:10.1016/j.placenta.2012.07.002 · Cited by 237 · see citing works
Asl, E. R., Amini, M. A., Najafi, S., Mansoori, B., Mokhtarzadeh, A., Mohammadi, A., Lotfinejad, P., Bagheri, M., Shirjang, S., Lotfi, Z., et al. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119499 · Cited by 232 · see citing works
Ineffective delivery of diet-derived microRNAs to recipient animal organisms
Snow, J. W., Hale, A., Isaacs, S. K., Baggish, A. L., & Chan, S. Y. (2013) · RNA Biology · doi:10.4161/rna.24909 · Cited by 234 · see citing works
Self-citationOxygen Sensing and Homeostasis
Prabhakar, N. R., & Semenza, G. L. (2015) · Physiology · doi:10.1152/physiol.00022.2015 · Cited by 222 · see citing works
Kiyuna, L. A., Albuquerque, R. P. E., Chen, C., Mochly‐Rosen, D., & Ferreira, J. C. B. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.019 · Cited by 225 · see citing works
Fumarate is a terminal electron acceptor in the mammalian electron transport chain
Spinelli, J. B., Rosen, P. C., Sprenger, H.-G., Puszynska, A. M., Mann, J. L., Roessler, J. M., Cangelosi, A. L., Henne, A., Condon, K. J., Zhang, T., et al. (2021) · Science · doi:10.1126/science.abi7495 · Cited by 221 · see citing works
Cheng, X., Ku, C.-H., & Siow, R. C. M. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.025 · Cited by 217 · see citing works
Kelly, T. J., Souza, A. L., Clish, C. B., & Puigserver, P. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01242-10 · Cited by 218 · see citing works
AMPK–mTOR Signaling and Cellular Adaptations in Hypoxia
Chun, Y., & Kim, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189765 · Cited by 209 · see citing works
MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines
Grosso, S., Doyen, J., Parks, S. K., Bertero, T., Paye, A., Cardinaud, B., Gounon, P., Lacas‐Gervais, S., Noël, A., Pouysségur, J., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.71 · Cited by 216 · see citing works
Cross Talk of Combined Gene and Cell Therapy in Ischemic Heart Disease
Ong, S., Lee, W. H., Huang, M., Dey, D., Kodo, K., Sánchez-Freire, V., Gold, J. D., & Wu, J. C. (2014) · Circulation · doi:10.1161/circulationaha.113.007917 · Cited by 213 · see citing works
Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria
Thomas, L. W., & Ashcroft, M. A. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03039-y · Cited by 211 · see citing works
MitomiRs in human inflamm-aging: A hypothesis involving miR-181a, miR-34a and miR-146a
Rippo, M. R., Olivieri, F., Monsurrò, V., Prattichizzo, F., Albertini, M. C., & Procopio, A. D. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.002 · Cited by 209 · see citing works
Hypoxia-inducible factors and their roles in energy metabolism
Goda, N., & Kanai, M. (2012) · International Journal of Hematology · doi:10.1007/s12185-012-1069-y · Cited by 213 · see citing works
Oxygen availability and metabolic reprogramming in cancer
Xie, H. J., & Simon, M. C. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.799973 · Cited by 203 · see citing works
Roles of microRNA on cancer cell metabolism
Chen, B., Li, H., Zeng, X., Yang, P., Liu, X., Zhao, X., & Liang, S. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-228 · Cited by 205 · see citing works
Yuan, G., Khan, S. A., Luo, W., Nanduri, J., Semenza, G. L., & Prabhakar, N. R. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22640 · Cited by 201 · see citing works
Oxidative Stress and MicroRNAs in Vascular Diseases
Magenta, A., Greco, S., Gaetano, C., & Martelli, F. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140917319 · Cited by 194 · see citing works
Cui, H., Seubert, B., Stahl, E., Dietz, H., Reuning, U., Leon, L. M., Ilié, M., Hofman, P. M., Nagase, H., Mari, B. P., et al. (2014) · Oncogene · doi:10.1038/onc.2014.300 · Cited by 190 · see citing works
The iron-sulfur cluster assembly machineries in plants: current knowledge and open questions
Couturier, J., Touraine, B., Briat, J., Gaymard, F., & Rouhier, N. (2013) · Frontiers in Plant Science · doi:10.3389/fpls.2013.00259 · Cited by 189 · see citing works
Disorders of cancer metabolism: The therapeutic potential of cannabinoids
Sun, D., Li, X., Nie, S., Liu, J., & Wang, S. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113993 · Cited by 187 · see citing works
Mitochondrial metabolism in pulmonary hypertension: beyond mountains there are mountains
Culley, M. K., & Chan, S. Y. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120847 · Cited by 178 · see citing works
Self-citationMolecular Mechanisms of High-Altitude Acclimatization
Mallet, R. T., Burtscher, J., Pialoux, V., Pasha, Q., Ahmad, Y., Millet, G. P., & Burtscher, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021698 · Cited by 185 · see citing works
The Role of Hypoxia-Induced miR-210 in Cancer Progression
Dang, K., & Myers, K. A. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16036353 · Cited by 177 · see citing works
Qiao, Y., Liang, L., Guo, W., Zha, R., Tian, Q., Huang, S., Yao, J., Ding, J., Bao, M., Ge, C., et al. (2010) · Hepatology · doi:10.1002/hep.24614 · Cited by 175 · see citing works
McCormick, R., Blick, C., Ragoussis, J., Schoedel, J., Mole, D. R., Young, A. C., Selby, P. J., Banks, R. E., & Harris, A. L. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.56 · Cited by 175 · see citing works
Mutharasan, R. K., Nagpal, V., Ichikawa, Y., & Ardehali, H. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01080.2010 · Cited by 175 · see citing works
Qi, J., Qiao, Y., Wang, P., Li, S., Zhao, W., & Gao, C. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.03.011 · Cited by 170 · see citing works
MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain
Zeng, L., He, X., Wang, Y., Tang, Y., Zheng, C., Cai, H., Liu, J., Wang, Y., Fu, Y., & Yang, G. (2013) · Gene Therapy · doi:10.1038/gt.2013.55 · Cited by 168 · see citing works
MicroRNA-210 Controls Mitochondrial Metabolism and Protects Heart Function in Myocardial Infarction
Song, R., Dasgupta, C., Mulder, C., & Zhang, L. (2022) · Circulation · doi:10.1161/circulationaha.121.056929 · Cited by 168 · see citing works
Circulating MicroRNAs and Aerobic Fitness – The HUNT-Study
Bye, A., Røsjø, H. R., Aspenes, S. T., Condorelli, G., Omland, T., & Wisløff, U. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057496 · Cited by 166 · see citing works
Multiple functions of hypoxia-regulated miR-210 in cancer
Qin, Q., Furong, W., & Li, B. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-33-50 · Cited by 166 · see citing works
Hypoxia-regulated microRNAs in human cancer
Shen, G., Li, X., Jia, Y.-F., Piazza, G. A., & Xi, Y. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.195 · Cited by 164 · see citing works
The VHL-dependent regulation of microRNAs in renal cancer
Neal, C. S., Michael, M., Rawlings, L. H., der Hoek, M. B. V., & Gleadle, J. (2010) · BMC Medicine · doi:10.1186/1741-7015-8-64 · Cited by 164 · see citing works
MitomiRs delineating the intracellular localization of microRNAs at mitochondria.
Bandiera, S., Mategot, R., Girard, M., Demongeot, J., & Henrion-Caude, A. (2013) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2013.06.013 · Cited by 148 · see citing works
Role of microRNAs in Lung Development and Pulmonary Diseases
Sessa, R., & Hata, A. (2013) · Pulmonary Circulation · doi:10.4103/2045-8932.114758 · Cited by 156 · see citing works
Ranchoux, B., Harvey, L. D., Ayon, R. J., Babicheva, A., Bonnet, S., Chan, S. Y., Yuan, J. X. ‐., & Pérez, V. D. J. (2017) · Pulmonary Circulation · doi:10.1177/2045893217752912 · Cited by 156 · see citing works
Self-citationMicroRNAs: crucial regulators of placental development
Hayder, H., O’Brien, J. A., Nadeem, U., & Peng, C. (2018) · Reproduction · doi:10.1530/rep-17-0603 · Cited by 157 · see citing works
Burtscher, J., Millet, G. P., Place, N., Kayser, B., & Zanou, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126479 · Cited by 158 · see citing works
Acclimatization of skeletal muscle mitochondria to high‐altitude hypoxia during an ascent of Everest
Levett, D. Z. H., Radford, E. J., Menassa, D. A., Graber, E. F., Morash, A. J., Hoppeler, H. H., Clarke, K., Martín, D., Ferguson‐Smith, A. C., Montgomery, H., et al. (2011) · The FASEB Journal · doi:10.1096/fj.11-197772 · Cited by 155 · see citing works
Kim, J. H., Park, S., Song, S.-Y., Kim, J. K., & Sung, J.-H. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.117 · Cited by 152 · see citing works
Giraud‐Billoud, M., Rivera‐Ingraham, G. A., Moreira, D. C., Burmester, T., Castro‐Vazquez, A., Carvajalino-Fernández, J. M., Dafré, A. L., Niu, C., Tremblay, N., Paital, B., et al. (2019) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2019.04.004 · Cited by 150 · see citing works
Nuclear factor-κB, p53, and mitochondria: regulation of cellular metabolism and the Warburg effect
Johnson, R., & Perkins, N. D. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.04.002 · Cited by 147 · see citing works
Responses to reductive stress in the cardiovascular system
Handy, D. E., & Loscalzo, J. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.006 · Cited by 147 · see citing works
Self-citation
- Authors
- Chan, S. Y., Zhang, Y.-Y., Hemann, C., Mahoney, C. E., Zweier, J. L., & Loscalzo, J.
- Affiliations
- Harvard University (US)
- The Ohio State University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Loscalzo, Joseph
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 10
- Issue
- 4
- Pages
- 273-284
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2759401
- OpenAlex
- W2087408461
- Cited by
- 702
- References
- 37
- Citations by year
- 2026: 33 · 2025: 44 · 2024: 30 · 2023: 24 · 2022: 45 · 2021: 73 · 2020: 44 · 2019: 50 · 2018: 29 · 2017: 51 · 2016: 35 · 2015: 38 · 2014: 59 · 2013: 60 · 2012: 39
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hv28178-12-0-0)
- U.S. Public Health Service (P01 81587)
- National Heart, Lung, and Blood Institute (HL61795, K08HL096834, U54HL070819, P01HL081587, N01-HV-028178, R21HL089734, R01HL061795, R37HL061795)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Keywords
- miR-210, iron-sulfur cluster assembly, hypoxia, mitochondrial metabolism, mitochondrial respiration, pulmonary artery endothelial cells, complex I, aconitase, iron-sulfur proteins
- MeSH terms
- Animals, Hypoxia, Cells, Cultured, Gene Expression Regulation, Humans, Iron-Sulfur Proteins, Mitochondria, Oxygen Consumption, Mice, Knockout, MicroRNAs, Endothelial Cells, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Caspase 3, Caspase 7
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
